The objective is to determine the mechanisms leading to sex-linked anemia (sla), hereditary microcytic anemia (mk), the Belgrade anemia (b), and the mottled trait (Mo), in order to identify genetically determined steps in mammalian iron and copper metabolism and erythropoiesis. The studies of sla and mk will include the chromatographic separation, identification and quantitation of iron-binding proteins in the duodenal mucosa, and the investigation of placental iron transfer by measuring neonatal or fetal Fe59 retention following the maternal administration of radio-iron during gestation. The effect of maternal genotype on fetal phenotype will be examined using the techniques of ovarian and blastocyst transplantation. The studies of the Belgrade anemia will include the in vitro uptake and utilization of iron by erythroid cells and the in vivo and in vitro synthesis of globin. Erythroid cells will be examined for the presence of functional mRNA using the wheat germ cell free system. The hematologic and iron status of normal rats will be manipulated to determine whether the copper metabolism abnormality of b/b animals can be reproduced. The hematologic status of affected male (MoBr/Y), heterozygous female (MoBr/plus) and normal mice will be compared and the effect of copper treatment assessed. Studies of copper metabolism will include the plasma clearance and hepatic uptake of radio-copper and the chromatographic separation and quantitation of copper binding substances in the intestinal mucosa.